Cytoglobin is a recently identified member of the mammalian globin family that is expressed in neuronal cells in the central and peripheral nervous system where its physiological role remains to be determined. In the current study, we demonstrate that a cytoglobin-green fluoresecent protein (GFP) fusion protein when expressed in the human neuronal cell line TE671 has a nuclear localization in a subpopulation of transfected cells (approximately 15%). Furthermore, the cytoglobin-GFP fusion protein but not GFP alone significantly reduced the induction of intracellular reactive oxygen species as assessed by oxidation of the redox-sensitive probe dichlorofluorescein following treatment with non-cytotoxic concentrations of the pro-oxidant Ro19-8022. In addition, expression of cytoglobin-GFP also afforded cytoprotection from Ro19-8022-induced oxidative DNA damage as assessed by the Fpg-modified comet assay. In conclusion, the current study provides evidence supportive of a role for cytoglobin in cytoprotection of neuronal cells from oxidative-related damage, for example, during ischaemic reperfusion injury following hypoxia.